Beam, Elena

AbstractGraft‐versus‐hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5–99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin‐resistant enterococci and gram‐negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia—these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired. image

Abstract Background Corynebacterium periprosthetic joint infection (PJI) is a poorly described infectious syndrome. Prior studies included cases of polymicrobial infections. This series describes the clinical characteristics, management, and outcomes of monomicrobial Corynebacterium PJI. Methods We queried the Mayo Clinic Total Joint Registry for cases of monomicrobial Corynebacterium knee and hip PJI in adults (age ≥18 years) between 2010 and 2019. Results A total of 20 (1%) out of 2067 PJI cases met our inclusion criteria. Most were males (55%), and the median age was 64 years. Seventy percent had chronic symptoms (>4 weeks). PJI was delayed to late (>3 months postimplantation) in 90%. Three species were identified: C. striatum (70%), C. jeikeium (20%), and C. amycolatum (10%). All tested isolates were susceptible to vancomycin (100%) and linezolid (100%), and most had a minimum inhibitory concentration ≤0.06 mcg/mL to daptomycin (75%). Other agents were less reliable, with high resistance to oral agents commonly used for suppression. Nineteen patients were treated: 37% debridement and implant retention (DAIR), 47% 2-stage exchange, and 16% resection without reimplantation. Of these, failure occurred in 29%, 11%, and 0%, respectively. Conclusions Corynebacterium PJIs pose a therapeutic challenge due to limited antimicrobial armamentarium and undefined optimal surgical intervention. Vancomycin and linezolid remain the most reliable agents for treatment. DAIR may be attempted for acute PJI, but verification of durable chronic suppression options will be critical for this approach.

Abstract Background Based on expert opinion, solid organ transplant recipients from donors with bacteremia are treated with 7-14 days of pre-emptive antibiotic therapy (PAT). However, studies addressing necessity, optimal duration of therapy, and outcomes in kidney transplant recipients (KTR) are lacking. Methods We retrospectively reviewed all kidney transplants performed at our institution from 01/01/2015-01/01/2021 to identify those cases where matched deceased donors had positive blood cultures. Bacteremia was defined per CDC criteria. We analyzed rate of infection in the KTR with the same organism identified in the donor blood culture within 30 days of transplantation. Results A total of 56 KTRs with donor positive blood cultures were identified. Demographic data are summarized in Table 1. Twenty of 56 cases (35.8%) had bacteremia and 36 (64.2%) had organisms classified as common commensals. The most common organisms in the bacteremia group were Gram-negative bacteria (12/20) and Staphylococcus aureus (6/20). Most common commensals were coagulase-negative staphylococci (26/36) (Table 2). All KTR received preoperative antibiotics at the time of transplantation, primarily cefazolin (15/20), and vast majority received TMP/SMX prophylaxis, for Pneumocystis jirovecii, post-transplant (19/20). PAT was administered in 70% (14/20) cases of bacteremia for a median of 8.5 days (IQR 7-14), while six cases were left untreated (Table 2). In contrast, majority of cases with common commensals were not treated (75%, 27/36). Of the cases treated (9/36), median duration of therapy was 7 days (IQR 5-14). No cases of infection with the same organism identified in the donor blood culture were reported in KTR within 30 days of transplantation. Conclusion KTR donors with bacteremia who were treated received a median of 8.5 days of PAT with no instances of breakthrough infection. In contrast, majority of donor blood cultures with organisms classified as common commensals were not treated and did well. Future studies are needed to assess whether perioperative antibiotics coupled with TMP/SMX prophylaxis post-transplantation are sufficient in select cases of transplantation from donors with bacteremia. Disclosures All Authors: No reported disclosures

Abstract Background Nocardia more commonly causes infection in immunocompromised individuals, notably with a relapse rate of approximately 5%. Solid organ transplant recipients will often receive post-treatment prophylaxis as the underlying immunosuppression is unable to be completely removed. However, data supporting this practice is sparse. We sought to evaluate recurrence of nocardiosis in solid organ transplant recipients, specifically evaluating the role of post-treatment prophylaxis. Methods We conducted a retrospective cohort study of solid organ transplant (SOT) recipients at our medical center diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy. Patients were excluded if they had not yet completed therapy, died prior to completing therapy, or there was no post-therapy follow-up. The primary outcome was Nocardia recurrence. Continuous variables were presented as mean or median with interquartile range (IQR). Results 108 patients meeting inclusion criteria were analyzed. 72 (66.7%) were male and median age was 60 years (IQR 52-65). Most common SOT types were kidney (47.2%), heart (17.6%), kidney-pancreas (11.1%), and lung (11.1%). Median time from transplantation to diagnosis of nocardiosis was 396 days (IQR 154-1071). Most common sites of infection were lung (88.0%), skin (16.7%), brain (13.9%), and blood (6.5%). Multi-organ infection was present in 22.2% and 24.1% were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at diagnosis. Post-treatment prophylaxis was utilized in 55 (50.9%) patients (Table 1). TMP-SMX was the most common prophylaxis (87.3%; Figure 1). Four patients experienced Nocardia recurrence, 2 of which were receiving TMP-SMX prophylaxis at time of relapse (Table 2). These were dosed as double strength tablet daily and weekly, respectively. Median time from treatment completion to relapse was 255.5 days (range 107-871). Figure 1. Post-Treatment Prophylaxis Regimens for Nocardia in 55 Patients Conclusion Nocardia recurrence in solid organ transplant recipients is an uncommon occurrence. Double strength daily and weekly TMP-SMX prophylaxis does not appear to be entirely protective and relapse may be dependent upon other factors such as primary treatment length. Further study into the use of post-treatment prophylaxis is warranted. Disclosures All Authors: No reported disclosures

AbstractBackgroundImmunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis.MethodsWe conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6 months of posttherapy follow‐up. The primary outcome was Nocardia recurrence, which included relapse and reinfection.ResultsOne hundred two patients met inclusion criteria. Sixty‐six (64.7%) were male and mean age was 58.6 ± 11.7 years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney‐pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. Trimethoprim‐sulfamethoxazole (TMP‐SMX) single‐strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, three of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p = .011), chronic lung disease (p = .032), and treatment ≤120 days (p = .006). Time from treatment completion to recurrence ranged from 107 to 875 days.ConclusionsNocardia recurrence in SOT recipients is an uncommon event. TMP‐SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted.

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with poor outcomes. Estimated risk of 1‐year IFI in heart transplant recipients is 3.4–8.6% with risk factors inconsistently identified in previous studies. The role of antifungal prophylaxis is unclear. The transplant program at Mayo Clinic provides 6 months of universal azole prophylaxis for those heart transplant recipients in Arizona. We sought to define risk factors for 1‐year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing heart transplantation at Mayo Clinic from January 2000 to March 2019. We analyzed demographics, details of transplant hospitalization, antifungal prophylaxis, and fungal infection. Multivariable Cox analyses were performed to identify risk factors of 1‐year IFI and impact of IFI on posttransplant mortality. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62). A total of 444 patients received antifungal prophylaxis. Over 1‐year follow‐up, 62 patients developed IFI with a cumulative incidence of 6.4%. In multivariable analysis, factors associated with IFI were renal replacement therapy (RRT) (HR 3.24, 95% CI 1.65–6.39), allograft rejection (HR 2.33, 95% CI 1.25–4.34), and antifungal prophylaxis (HR 0.32, 95% CI 0.11–0.96). RRT was also associated with invasive mold infection (HR 3.00, 95% CI 1.29–6.97). Conclusions RRT and allograft rejection after transplantation are associated with 1‐year IFI, and RRT is also associated with invasive mold infection. Antifungal prophylaxis appears to be protective and further study is needed in the heart transplant population.

AbstractBackgroundBamlanivimab and casirivimab-imdevimab are authorized for emergency use treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients at high risk for developing severe disease or hospitalization. Their safety and efficacy have not been specifically evaluated in solid organ transplant recipients.MethodsWe retrospectively reviewed solid organ transplant recipients who received monoclonal antibody infusion for COVID-19 at Mayo Clinic sites through January 23, 2021. Outcomes included emergency department visit, hospitalization, mortality, and allograft rejection.ResultsSeventy-three patients were treated, most commonly with bamlanivimab (75.3%). The median age was 59 years, 63% were male, and the median Charlson comorbidity index was 5. Transplant type included 41 kidney (56.2%), 13 liver (17.8%), 11 heart (15.1%), 4 kidney-pancreas (5.5%), 2 lung (2.7%), 1 heart-liver, and 1 pancreas. Eleven (15.1%) patients had an emergency department visit within 28 days of infusion, including 9 (12.3%) who were hospitalized for a median of 4 days. One patient required intensive care unit admission for a nonrespiratory complication. No patients required mechanical ventilation, died, or experienced rejection. Ten adverse events occurred, with 1 seeking medical evaluation. Hypertension was associated with hospital admission (P < .05), while other baseline characteristics were similar. The median time from symptom onset to antibody administration was 4 days in nonhospitalized patients compared with 6 days among hospitalized patients (P < .05).ConclusionsMonoclonal antibody treatment has favorable outcomes with minimal adverse effects in solid organ transplant recipients with mild to moderate COVID-19. Earlier administration of monoclonal antibody therapy appears to be more efficacious.

AbstractInvasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve.

Abstract Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures